Model Systems Core Project Summary/Abstract The Model Systems Core (MSC) will leverage the institutional strengths of Washington University School of Medicine (WUSM) in genetics, neuroscience, bioinformatics and neuroimaging to address key questions on the causes and treatments of IDD with particular reference to genetic abnormalities and environmental factors. The MSC will be organized into two units ? the Cellular Models Unit (CMU) and the Animal Assessments Unit (AAU), the latter being composed of three subunits including Animal Behavior, Neuropathology, and Neurophysiology. Through its team of interactive scientists, the MSC will pursue its specific aims by providing seamless expertise, resources, and assessments to committed WUSM investigators for the purpose of: (1) promoting the discovery of the basic molecular and cellular pathways shared by diverse causes of IDD; (2) determining the neural signatures associated with IDD at the neural circuit level and whole brain; (3) characterizing core neurobehavioral features of IDD and clarifying their causal origins; and (4) developing interventions to ameliorate the effects of genetic or environmental insults on the developing brain. To achieve these goals, the MSC will use an integrated model systems approach to synergize the strengths of its own units as well as those of the Clinical Translational Core and the Developmental Neuroimaging Core. Additional aims for each unit will also be operative. For example, reprogrammed somatic cell models of human disorders provide fundamental insights into biological pathways as well as disease processes; therefore, the MSC will now offer renewable patient-derived human IDD cellular models to link genetic alterations with disease mechanisms and phenotype via the CMU. The MSC will also continue to provide consultation and comprehensive assessment of brain structure, pathology, physiology and behavior of IDD animal models through the AAU. Reaching across cores, the CMU will work closely with the Clinical Translation Core?s human genomic characterization unit to develop IDD patient registries that will be directly used as a recruitment source for derivation of patient-derived cellular models. Similarly, the AAU depends upon the Developmental Neuroimaging Core for imaging relevant preclinical models to investigate mechanisms underlying developmental pathology potentially providing a bridge to clinical studies. Using these strategies, the overarching mission of the MSC is to identify new treatments, biomarkers and/or interventions that can prevent or reduce the impact of IDD-linked diseases. As more genomic data becomes available and WU investigators capitalize on this information, another critical role for the MSC will be the integration of new and existing information across the IDDRC@WUSTL cores and other existing facilities within the University.